Chemistry – Page 14 – David Bradley

Dental Lead, Lung Cancer and Monopoles

This week’s ezines on SpectroscopyNOW are now live, featuring a breath test for lung cancer, magnetic monopoles, a way to boost fuel cells, and reducing toxic waste from dental surgeries.

Extracting the dental lead – Lead contamination in the black paper used to mask dental X-ray paper has been determined for the first time using AAS. The worrying results suggest that the used material represents an environmental waste problem requiring pre-treatment before disposal.

I asked the researchers to outline the importance of their study. Team leader Debora Guedes told me that, “There are still more than 600 million packets of intraoral film exposed each year in the USA alone, and much more elsewhere in the world. The volume of potential waste materials is significant,” she says.

She pointed out that while attention has previously been given to the disposal of the lead foil used against backscatter radiation that can fog an X-ray image and also to avoiding lead-lined boxes to store intraoral dental X-ray film, lead contamination of the black paper used to help exclude light from the film, or the paper or plastic wrapping of the film and lead foil has been ignored entirely, she adds. “This study is an important public health contribution as it indicates that this neglect is of potential importance,” Guedes told me.

A breather for lung cancer suspects – Researchers in Israel have used cheminformatics methods to “train” an array of gold-nanoparticle sensors to rapidly distinguish between the out breath of lung cancer patients and that of healthy individuals.

Monopoles apart – Four research papers, two of which were published in the journal Science, this week, and two submitted to the physics preprint archive, suggest that a long-sought icon of fundamental physics has finally been discovered – the magnetic monopole. This fundamental research could have enormous potential in materials research, nanotechnology, and eventually instrumentation.

Fuelling nanotube potential – X-ray diffraction and X-ray photoelectron spectroscopy have been used to analyse semimetallic titanium dioxide nanotubes with potential in fuel cell technology.

50 Million Chemicals and Counting

UPDATE: Sept 8 – Compound 50m in the CS Registry is a novel arylmethylidene heterocycle with analgesic properties called (5Z)-5-[(5-fluoro-2-hydroxyphenyl)methylene]-2-(4-methyl-1-piperazinyl)-4(5H)-thiazolone. (Registry number 1181081-51-5).

According to an email I received from a CAS spokesman, “The number itself represents an important milestone both for researchers and CAS, but even more significant is the pace of scientific discovery around the world.” Roger Schenck, Manager of the Content Planning Department at CAS, adds that, “More scientific literature is being published and we have noticed an explosive growth of patent literature since 1998 that accounts for the rapid growth of substance information available.”

cas-1181081-51-5 By contrast, it took 33 years for CAS to register 10 million compounds, a milestone reached in 1990.

It’s intriguing to think that two decades after I wrote a news item (very early in my career) discussing the announcement of that 10 millionth entry for one of the chemistry trade magazines, that CAS should be recording its 50 millionth substance. Indeed, it’s a mere nine months since it announced the 40 millionth.

Apparently, the predominant source of this new chemical substance information is the global patent literature. Several years ago, patents accounted for approximately 20 percent of the substance information added to the registry. Today, that number is closer to 70 percent. It was that statement that intrigued me most.

But, I wonder…if they’re scraping patents on such a vast scale, is the addition of a few extra million entries actually representative of technological advance? An alternative explanation is that it simply shows how clever patent attorneys are at working with chemists to couch their claims in such imaginative ways to envelope a whole chemical space in a single sentence.

The increase could be a real indication that researchers increasingly are thinking in terms of monetizing their discoveries, and doing so much earlier in the research process. It could of course be due to increasing research around the world or maybe it’s driven by demand for more advanced electronics and the need for materials for such devices. There are also increasing demands from medical and pharmaceutical research. But, could this have lead to so many million more compounds?

I’m sure it’s not just CAS running a “stamp collecting” business, there has been research demonstrating molecular diversity in the collection.

Schenck confirmed that molecular diversity is something CAS takes seriously. “In regards to molecular diversity in CAS Registry, CAS scientists recently published an article in the Journal of Organic Chemistry on structural diversity among the 24 million organic substances in Registry at the time and may help to answer in-depth diversity questions,” he says.

He also pointed out that CAS monitors the literature as it is published and selects substances in the literature that meet its criteria. To be added the structure must come from a reputable source, including but not limited to patents, journals, chemical catalogues, and selected substance collections on the web. It has to have been described in largely unambiguous terms, characterized by physical methods or described in a patent document example or claim. It also has to be consistent with the laws of atomic covalent organization.

There are also some subtle legislative effects at play too, as Schenck explains:

In the academic community, such activities were greatly enhanced by U.S. legislation passed in 1980, the Bayh-Dole Act, which requires that universities actively seek commercialization for federally-funded research.

The 50-millionth compound will be an interesting milestone. Its identity will not be revealed until tomorrow. It’s probably not going to be a magic bullet for disease or an environmental panacea, but it’s not going to be a trivial compound either. Just how interesting it is will be determined over time, after all there are few compounds without any intrinsic interest.

It would be a happy coincidence if this 50 millionth entry just happened to be something chemically fascinating, to drive innovation from cancer research and nanotechnology to alternative fuel vehicles, cell phones and more. I suspect it will be a little more mundane, but 50 million entries in any collection is a significant milestone regardless.

Lipkus, A., Yuan, Q., Lucas, K., Funk, S., Bartelt, W., Schenck, R., & Trippe, A. (2008). Structural Diversity of Organic Chemistry. A Scaffold Analysis of the CAS Registry The Journal of Organic Chemistry, 73 (12), 4443-4451 DOI: 10.1021/jo8001276

Alchemist Checks Oxy Cholesterol Levels

copper-alchemist The Alchemist this week learns how fluorine chemistry is blooming, how to melt proteins, and how cholesterol is all about the good, the bad, and the oxy. Also this week, a technique borrowed from organic LED fabrication could lead to a new way to manufacture tiny inorganic LEDs for next generation displays, while a conductive flip has been observed with clusters of atoms close to absolute zero. Finally, the American Chemical Society announces this years previously unsung chemical heroes from across the industry.

Previously on ChemWeb, we heard rumors of silicon neurons and the coming cyborg age, he discovers that a compound that leads to ovine Cyclops has now been synthesized for cancer drug research, and how chicken poop down on the shooting range could help solve the problem of lead in the soil. Also, in the news, a new type of fuel cell for truckers that reduces their emissions during rest periods and the increasing cost in water of producing bioethanol. Finally, a major award for a generic pharmacologist.

Swine Flu and Glutathione Supplements

Could a simple dietary change that increases glutathione, or indeed supplementation with this tripeptide be all you need to boost your immune system and ward of influenza?

Evidence mounted for glutathione itself in 2000, when Emory University researchers led by Dean Jones reported that a lozenge or oral spray containing glutathione might help prevent infection with influenza. Trials in humans had not been carried out but details were reported in Free Radical Biology and Medicine and elsewhere.

If glutathione is actually effective against influenza infection, and it may well not be, then it would presumably have to be present at the infection site – mouth and nose and upper respiratory tract. No definitive clinical trials have proven efficacy one way or the other yet.

FRIEL, H., & LEDERMAN, H. (2006). A nutritional supplement formula for influenza A (H5N1) infection in humans? Medical Hypotheses, 67 (3), 578-587 DOI: 10.1016/j.mehy.2006.02.040

Hot, Tardy Alchemist

copper-alchemist Bit late with the update for The Alchemist this week, had so much else to talk about before a slot was available, there was also the matter of our family vacation, hope readers find the info current enough to be of interest.

The Alchemist recently learned that music could be the key to the smooth running of a lab-on-a-chip, while tweaking quantum dots for the light show might be possible through physical rather than chemical changes. Imprinted polymers could remove vitamin B2 from beer giving it a longer-lasting flavor, we learn, while Japanese scientists have sniffed out the chemical basis of at least one form of aromatherapy. In the analytical arena, a simple enzyme-based test has been devised for spotting melamine adulteration in milk samples. Finally, the establishment of the InChI Trust will promote the use of chemical string theory for structure searching.

My Intute Spotlight column migrated to the all-new Hot Topics section on Intute while I was on holiday, so you can access my physical words for August here:

Inorganic oil – The stock explanation for the origins of crude oil and natural gas is that these hydrocarbons are the end product of millions of years of geochemical processing of long-dead sea creatures. But, these materials might also be found much deeper in the Earth’s mantle and may have a non-organic origin hinting at a controversial mechanism for a partial replenishment of reserves.

Over and Oort on the comet’s tale – An enormous asteroid or comet smashing into the Earth 65 million years ago killed off the dinosaurs. But, according to a new study by US scientists, published in the wake of an impact event on Jupiter, cometary collisions with Earth probably didn’t cause any more than one other extinction event during life’s history.

Nano X-ray tube – Material scientists, medical physicists, and cancer biologists will all benefit from the development by US researchers of a low-cost X-ray tube packed with sharp-tipped carbon nanotubes.

How to find new drugs for malaria

German researchers have used the powerful analytical technique of X-ray diffraction to home in on an important metabolic reaction used by all pathogenic bacteria and the malaria parasite. The detailed structure of the IspH enzyme active site they revealed, which resembles a shamrock in shape, and has an Fe-S cluster at its core, could offer a promising new target for novel antibiotics that might stave off bacterial resistance.

More details on the research can be found in my XRD column on SpectroscopyNOW this week. Meanwhile, I asked team leader Michael Groll of the Technische UniversitÃ¤t MÃ¼nchen (TUM), to expand on the implications of the work.

What is the next step now that you’ve characterized the active site?

The structure allows us to perform modeling and so look for attractive ligands and putative inhibitors of the enzyme. Furthermore, we need to understand how substrates access the enzyme, docking and release. It looks like there is a major structural rearrangement, a so-called induced-fit mechanism, between the open and the closed (ligand bound) state of the IspH enzyme.

It would be interesting to get further insights into this mechanism which might allow us to get a comprehensive overview of the catalyzed specific reaction. Since the reaction of the substrate is a reduction, the FeS-cluster in the enzyme gets oxidized, we also need to understand the mechanism of enzymatic reduction of this FeS-cluster.

How might drug targets be developed for this enzyme?

Molecular modeling and high throughput screening (HTS) will be key. It would be important to get structures of various ligands including substrate and product (currently we have only modeled the substrate, which we would like to experimentally verify by the complex structure). These new compounds and structures definitely will serve as lead structures for drug development!

Surely, bacteria will simply evolve resistance to those anyway?

Yes, that can be expected. Nevertheless, it should be mentioned that most bacteria become resistant to drugs, since they create enzymes to metabolize the drug or transport it out of the bacteria — this is nothing new. For Vancomycin, it took more than 7 years to see the first resistant strains. It is definitely worth looking for IspH inhibitors as putative new antibiotics. Moreover, it is an attractive new target, because IspH exists only in bacteria, Plasmodia and some plants, and not animals, which would mean a lower risk of side-effects.

GrÃ¤wert, T., Rohdich, F., Span, I., Bacher, A., Eisenreich, W., Eppinger, J., & Groll, M. (2009). Structure of Active IspH Enzyme from Provides Mechanistic Insights into Substrate Reduction Angewandte Chemie International Edition, 48 (31), 5756-5759 DOI: 10.1002/anie.200900548

Alchemist Taking the P

copper-alchemist The current issue of my Alchemist column on ChemWeb.com is now online:

The old alchemist’s trick of attempting to use urine as a starting material for all kinds of products could offer the twenty-first century a golden opportunity, we learn this week, while electrospinning DNA nanofibers might shed white light on new technologies without requiring a naked flame. If the alchemists were searching for everlasting life, then the discovery that a compound from Easter Island is a murine elixir may not come as a surprise. There’s also a sweet surprise for lovers of corn who are not persuaded by chemophobics to go “organic.” Turns out that the application of weedkiller to sweetcorn boosts the nutritional content of the yellow kernels. The melamine petfood scandal of 2007 and the more recent poisoning of infants in China thanks to adulterated dairy products has been investigated with a novel analytical technique that provides a baseline mark for unaffected children. Finally this week, clean fuels could emerge from a multimillion-dollar investment in the US.

Stinging Heavy Metal Resistance

Head-banging science news with a spectroscopic bent from my latest posts on the SpectroscopyNOW ezines, live June 15.

A medical tale in the sting – The venom of the eusocial bee contains three novel antimicrobial compounds known as lasioglossins, which have been structurally characterised by NMR spectroscopy. The compounds offer a new avenue for developing new antibiotics that might defeat drug-resistant bacteria.

Marine surfactant soaks up heavy metal – Atomic absorption spectroscopy (AAS) and other techniques have been used to demonstrate the effectiveness of a natural surfactant molecule in removing heavy metals from solutions for potential bioremediation applications.

Topical resistance – Crystallography by UK scientists may have uncovered the mechanism by which quinolone drugs interact with DNA and bacterial topoisomerase and so point to a better understanding of how resistance to this class of drugs emerges in meningitis and pneumonia.

Exhausted grapes fit only for compost – Multivariate analysis of the physicochemical, chemical and biological parameters of winery and distillery composts could point the way to improving the use of these generally intractable waste materials.

Cannabis Cancer, Toxic Waste, Antibiotics

The latest science news with an analytical bent from yours truly, now available in the SpectroscopyNOW ezines:

Cannabis blow back – A highly sensitive new chemical test has allowed European scientists to obtain “convincing evidence” that marijuana smoke damages DNA in ways that could increase the risk of cancer.

Toxic shock – Researchers in Spain are evaluating the “ecotoxic” properties of hazardous and toxic wastes for the aquatic environment. They suggest that the ecotoxic profile of a given waste stream can be derived from a novel battery of bioassays using statistical techniques that reveal whether dangerous levels of compounds toxic to frogs and fish are present and whether or not uber-toxins* like dioxins are at unsafe levels.

Chemical directors – Chemistry often all about activation. Now, UK chemists have found a way to control and direct the activation of important molecules used to synthesise pharmaceutical and agrochemical products. Their work also provides new insights into how bond activation works.

Enzymic activity – Researchers have obtained the first three-dimensional crystal structure of an enzyme that contains iron and helps soil microbes fend off invaders and rivals. The enzyme hydroxyethylphosphonate dioxygenase (HEPD) used by the Streptomyces soil microbe could lead to new agricultural technology, chemical catalysts, and perhaps even novel antibiotics that defeat bacterial resistance to conventional drugs.

*Yes, I know the word toxin applied only to compounds naturally derived and that attaching the uber mock prefix to this word is probably also misplaced as dioxins have a much worse reputation than they deserve, but I couldn’t help myself and they are very poisonous.

Short, Sharp Alchemist

copper-alchemist Natural quasicrystals, graphene interconnects, and photo-powered nanomotors all come into view through The Alchemist’s eyeglass this week.

Also in view, is the finding that hydrogen peroxide is more than a bleach, it’s a marshal for white blood cells to flood to the body’s injury sites. Solar-powered humidity on tap might help solve pure water shortages in some arid parts of the world.

Finally, the ACS has named its Washington DC headquarters after Clifford & Kathryn Hach Building following a $33 million donation.

More…